1. Field of the Invention
The present invention relates to detecting and quantitatively measuring error causing parameters in fluid handling, particularly liquid aspirating and dispensing in a diagnostic analyzer. In particular, the present invention relates to detecting and quantifying bubbles.
2. Description of the Related Art
In many diagnostic analyzers, accurate aspiration or dispense of a sample or reagent is an important factor in determining dispensing accuracy and sample quality. Governmental regulatory agencies, such as the United States Food and Drug Administration have strict regulations requiring the accurate aspiration and dispense of a liquid due to the risks of incorrectly performing assays or misreporting a sample integrity result. If an error is detected, the sample must be disregarded and the analysis rerun at considerable time and expense. If the magnitude of the error were known, it would be possible in some instances to adjust the analysis, such as by adding more or less of another component, without the necessity of disregarding the sample and rerunning the analysis.
One significant error in aspirating or dispensing is that insufficient liquid is aspirated due to an error causing physical parameter, such as air or bubble aspiration. Therefore, it is important to detect insufficient aspiration or dispensing accurately before starting any analysis, such as assays or performing sample integrity measurements. In the case of error inducing bubbles, it is known that insufficient aspiration is more likely to occur when 1) there is too little liquid in the container, 2) the aspiration is too fast, and 3) when the liquid viscosity is too high. Other error inducing parameters can include clogs, clots, debris, foam, etc.
In a typical diagnostic analyzer, a pressure sensor, such as a transducer, is mounted between the piston pump and the liquid being aspirated, and the pressure variation in the aspiration process is monitored. It is generally known in the art that monitoring pressure during aspiration can be used to determine the occurrence of unintended aspiration of air. See, e.g., WO 97/22007. While known art, such as the '007 patent publication, describes detecting the presence of an error, such known art does not teach quantitatively measuring such errors. It is also known to monitor pressure during the dispense of a fluid to determine the amount of fluid dispensed. See, e.g., WO 98/45205.
A significant technical challenge in the art has been to determine the volume or quantitative error in aspirated liquid from the pressure signature because of the random noise generated by the free surface of aspirated liquid when the error causing parameter, such as air (or a bubble), is aspirated into the tip. The pressure signature is further confounded by vibration of the aspirated liquid inside the tip while the viscosity and surface tension are unknown.
Due to the geometry variations at the tip-container juncture, free surface instability, and vibration in the system, it is difficult to correlate the pressure signature to the volume of the air inside the tip of an aspirating or dispensing probe. Although a curve fitting with proper models could provide useful information for the fluid property, it remains a challenge to predict the quantity of error, such as air volume aspirated. In an ideal system, the pressure level at the end of the aspiration should directly represent the amount of liquid aspirated. However, the pressure level is confounded by the surface tension and the meniscus configuration at the end of the tip, which is impossible to obtain in an on site process. Measuring the weight of the aspirated tip to determine the amount of liquid actually aspirated is not realistically feasible in a clinical setting.
U.S. Pat. No. 6,913,933 describes a fluid dispensing algorithm for a variable speed pump driven metering system.
For the foregoing reasons, there is a need to be able to quantify error causing parameters during a fluid handling process, particularly in an aspirating or dispensing process as opposed to simply detecting the presence of an error, in order to determine the amount of liquid actually being handled. There is also a need to be able to adjust an analysis based on the actual amount of liquid being handled in order to reduce the number of analyses that must be rerun altogether. There is also a need for an increased improvement in the robustness or reliability of a system to make such error detection and measurements.